This application is a resubmission for the competitive renewal of CA59005, "Aspirin-Folate Prevention of Neoplastic Polyps," a double-blind, placebo-controlled factorial design clinical trial of the efficacy of aspirin and/or folate in the prevention of the recurrence of large bowel adenomas in subjects with a recent history of these tumors. The trial was motivated by recent epidemiological and experimental data suggesting that folic acid and non-steroidal anti-inflammatory drugs, including aspirin, have anti-neoplastic properties in the large bowel. Since neoplastic polyps (adenomas) are pre-malignant lesions in the bowel, they are appropriate endpoints for trials of these effects. The study began in 1994 as an investigation of aspirin alone. After supplemental funding was secured in 1995, the investigation was converted to a 2 x 3 factorial design with two agents: folate (placebo or 1 mg folate daily), and aspirin (placebo, 80 mg, or 325 mg daily). At study entry, subjects complete a medical/personal history questionnaire as well as a food frequency questionnaire. A blood sample is also collected at study entry and stored as a source of DNA and plasma for future research. Subjects initially enroll in a 3-month aspirin run-in period during which suitability for the study is assessed, i.e. tolerance to aspirin and adherence to study procedures. Every 4 months after randomization, subjects complete a questionnaire regarding compliance with study agents, use of medications and vitamin/mineral supplements, illnesses, and hospitalizations. Colonoscopic follow-up and study completion is planned for 3 years after the qualifying endoscopy. Subjects provide a second blood sample and a food frequency questionnaire at that time. In March, 1998, recruitment ended. At that time, total of 1406 subjects had entered the trial: 1028 were randomized, 268 were considered unsuitable for randomization and 110 were still in the 3-month run-period. To date, compliance of subjects with the study has been excellent; depending on time since randomization, 83 percent-90 percent of subjects are taking virtually all their study tablets. With the funds requested here, we anticipate completion of the treatment phase and initial statistical analyses. We also propose to measure urinary thromboxane B2, and red blood cell and serum folate near the time of study completion. These will be used as measures of compliance with study agents.